Ma Ming, Yang Xingxiao, Zhao Lianmei, Wang Xuexiao, Liu Lihua, Jiao Wenjing, Wei Yuanyuan, Shan Baoen
Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Department of Infection Management, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Oncol Lett. 2018 Apr;15(4):4649-4656. doi: 10.3892/ol.2018.7897. Epub 2018 Jan 29.
Celecoxib is a newly-identified nonsteroidal anti-inflammatory drug, which has been used to treat fever in clinical practice. Celecoxib has been demonstrated to suppress the viability of various human tumor cells. However, the effect of celecoxib on response of T-cell lymphoma to chemotherapy agents remains unclear. The aim of the present study was to investigate the effect of celecoxib on chemosensitivity of human T-cell lymphoma, and to address the underlying mechanism of action. The cytotoxicity of CDDP, epirubicin and VCR on Jurkat and Hut-78 cells treated with celecoxib was assessed by MTT assay, and the half-maximal inhibitory concentration (IC) value was calculated by Origin 75 software. The effect of celecoxib on apoptosis and intracellular concentration of Rhodamine-123 in Jurkat and Hut-78 cells was analyzed by flow cytometry. The expression of transcription factor p65 (p65), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) at mRNA and protein levels were detected by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Proliferation suppression rates and apoptosis levels were significantly increased in Jurkat and Hut-78 cells combined with celecoxib compared with those without celecoxib, when treated with CDDP, epirubicin and VCR. The IC values of the chemotherapy agents were lower in Jurkat and Hut-78 cells treated with celecoxib compared with those that were not. The apoptosis level, expression of Bax and the intracellular concentration of Rhodamine-123 were increased, whereas the expression of p65, Bcl-2, MDR1 and MRP1 were decreased, in celecoxib-treated Jurkat and Hut-78 cells compared with those without celecoxib treatment. These results indicated that celecoxib may enhance the sensitivity of T-cell lymphoma to chemotherapy drugs by inhibiting the expression of multidrug resistance (MDR)-associated proteins via downregulating the activity of the nuclear factor-κB signaling pathway, suggesting that celecoxib may improve the curative effect of chemotherapy drugs in T-cell lymphoma.
塞来昔布是一种新发现的非甾体抗炎药，已在临床实践中用于治疗发热。塞来昔布已被证明可抑制多种人类肿瘤细胞的活力。然而，塞来昔布对T细胞淋巴瘤对化疗药物反应的影响仍不清楚。本研究的目的是探讨塞来昔布对人T细胞淋巴瘤化疗敏感性的影响，并阐明其潜在的作用机制。通过MTT法评估顺铂、表柔比星和长春新碱对用塞来昔布处理的Jurkat和Hut-78细胞的细胞毒性，并使用Origin 75软件计算半数最大抑制浓度（IC）值。通过流式细胞术分析塞来昔布对Jurkat和Hut-78细胞凋亡及罗丹明-123细胞内浓度的影响。分别通过逆转录定量聚合酶链反应和蛋白质印迹法检测转录因子p65、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、多药耐药蛋白1（MDR1）和多药耐药相关蛋白1（MRP1）在mRNA和蛋白质水平的表达。当用顺铂、表柔比星和长春新碱处理时，与未使用塞来昔布的Jurkat和Hut-78细胞相比，联合使用塞来昔布的细胞增殖抑制率和凋亡水平显著增加。与未处理的细胞相比，用塞来昔布处理的Jurkat和Hut-78细胞中化疗药物的IC值更低。与未用塞来昔布处理的细胞相比，用塞来昔布处理的Jurkat和Hut-78细胞的凋亡水平、Bax表达及罗丹明-123细胞内浓度增加，而p65、Bcl-2、MDR1和MRP1的表达降低。这些结果表明，塞来昔布可能通过下调核因子-κB信号通路的活性来抑制多药耐药（MDR）相关蛋白的表达，从而增强T细胞淋巴瘤对化疗药物的敏感性，提示塞来昔布可能提高化疗药物对T细胞淋巴瘤的治疗效果。
